Interspecific somatic cell hybrids have been extensively used to expand our studies on the genetic basis of tumorigenesis. We have used somatic cell hybrids to identify and chromosomally map specific genes involved in oncogenesis and to construct cell lines carrying isolated genetic elements of this complex multi-gene system for their further characterization. Most recent studies on viral receptor genes have mapped receptor loci for ecotropic and MCF MuLVs to different chromosomes. Hybrids which lack specific receptor loci were used to describe the time course of virus induction for different endogenus proviral loci. Finally, somatic cell hybrids are being analyzed by blot hybridization with molecularly cloned probes to describe the chromosomal localization of proviral and other cancer-related loci. These studies have resulted in the localization of endogenous mouse mammary tumor viral (MMTV) loci to 2 mouse chromosomes and tumor-specific MMTV integrations to 4 mouse chromosomes. Xenotropic envelope-reactive sequences were mapped to almost all of the mouse chromosomes and a single provirus associated with the Bxv-1 induction locus was identified. Three loci representing tumor-specific ecotropic MuLV integration were mapped to chromosome 15. Finally, analysis of hybrids has provided specific map locations for various proto-oncogenes and for interferon structural genes.